Chiral phospholanes via chiral 1, 4-diol cyclic sulfates

ABSTRACT

This invention relates to novel chiral 1,4-diol cyclic sulfates and their use as precursors in the preparation of chiral phospholane ligands, and chiral complexes useful as catalysts for carrying out enantioselective reactions.

This is a divisional application of Ser. No. 07/978,215, file Jul. 27,1992, now U.S. Pat. No. 5,329,015, which is a divisional of applicationSer. No. 07/725,121, filed Jul. 02, 1991, now U.S. Pat. No. 5,171,892.

FIELD OF THE INVENTION

The invention relates to novel chiral 1,4-diol cyclic sulfates and theiruse as precursors in the preparation of chiral phosphines, includingnovel chiral bis(phospholanes). Chiral transition metal complexes ofthese chiral bis(phospholanes) are efficient catalysts for carrying outenantioselective reactions.

BACKGROUND OF THE INVENTION

The development of novel catalytic systems exhibiting unique reactivityand high enantioselectivity requires the synthesis of chiral ligands fortransition metals. Generally, some of the most successful chiral ligandshave been chelating phosphines possessing a C₂ symmetry axis.

Many of the chiral phosphines known in the art have at least two arylsubstituents on the phosphorous, rendering that center relativelyelectron poor. The mechanism of asymmetric induction using thesephosphines has been linked to the proper conformational relationshipbetween the phenyl groups on the phosphorous centers.

More recently, chiral phosphines having relatively electron richphosphorus centers have been reported. Brunner et al., Journal ofOrganometallic Chemistry, Vol. 328, pp 71-80 (1987) teach3,4-disubstituted phospholanes derived from tartaric acid having chloro,methoxy, or dimethylamino substituents. These were complexed withmanganese and rhodium and used as catalysts in the hydrogenation ofalpha-N-acetamidocinnamic acid. Relatively low optical yields of(S)-N-acetylphenylalanine of from 6.6% enantiomeric excess to 16.8%enantiomeric excess were obtained.

S. R. Wilson and A. Pasternak, Synlett, pp. 199-200, April 1990 describethe preparation of (2R,5R)-1-phenyl-2,5-dimethylphospholane and its usein an enantioselective Staudinger reaction (reduction of azides withphosphines). Here the chiral (2R,5R)-1-phenyl-2,5-dimethylphospholane isused as a stoichiometric reactant, not as a catalyst.

M. J. Burk et al, Organometallics, Vol 9, pp. 2653-2655 (1990) describea series of mono and bidentate 2,5-disubstituted phospholanes anddemonstrate their use as ligands in asymmetric catalysis. Rhodiumcomplexes bearing the disclosed phosphine ligands were prepared andtested as catalyst precursors for the enantioselective hydrogenation ofunsaturated substrates. The phosphorous atoms in the disclosed bisphospholanes are linked by two- or three-carbon methylene bridges.

M. J. Burk et al, Angewandte Chemie, International Edition in English,Vol 29, pp 1462-1464 (1990) disclose tris phospholane tridentate ligandswith C₃ symmetry.

U.S. Pat. No. 5,008,457 issued Apr. 16, 1991, discloses mono, bidentate,and tridentate phospholanes useful as transition metal ligands inasymmetric catalysis and processes for their preparation as in the abovetwo Burk et al. references.

Several references teach various synthetic routes for the preparation ofcyclic sulfites or cyclic sulfates. However, these contain no disclosurenor suggestions that the disclosed reaction sequence could be used toprepare symmetrical chiral 1,4-diol derived cyclic sulfites or 1,4-diolderived cyclic sulfates.

Y. Gao and K. B. Sharpless, J. Am. Chem. Soc., 110, 7538(1988) disclosedthe reaction of 1,2-diols, including some chiral 1,2-diols, with thionylchloride to form 5-membered ring cyclic sulfites which, upon oxidationwith NaIO₄ and catalytic RuCl₃, are converted to 5-membered ring cyclicsulfates.

B. M. Kim and K. B. Sharpless, Tetrahedron Lett., 30, 655(1989) reportfurther on the preparation and reactivity of 5-membered ring cyclicsulfates derived from 1,2-diols.

U.S. Pat. No. 4,924,007 discloses a process for the preparation of 5-and 6-membered ring cyclic sulfates from 1,2- and 1,3-diols by reactionwith concentrated sulfuric acid at 150° C. to 250° C.

U.S. Pat. No. 4,960,904 discloses a process for the preparation of 5-and 6-membered ring cyclic sulfates from 5- and 6-membered ring cyclicsulfites by oxidation.

Great Britain Patent 944,406 discloses a process for the preparation of5- and 6-membered ring cyclic sulfates from 1,2- and 1,3-diols byreaction with first, thionyl chloride to form 5- and 6-membered ringcyclic sulfites and second, an oxidizing agent.

J. Lichtenberger and J. Hincky, Bull. Chim. Soc. Fr, 1495(1961) describethe synthesis of a cyclic sulfate from 1,4-butanediol.

E. J. Lloyd and Q. N. Porter, Aust. J. Chem., 30, 569(1977) describe thesyntheses of cyclic sulfates from 1,4 -butanediol and 2,5-hexanediol.

N. Machinaga and C. Kibayashi, Tetrahedron Letters, Vol. 31, p. 3637(1990), describe the synthesis of an unsymmetrical, chiral 1,4-diolderived cyclic sulfate and the synthesis of an unsymmetrical, chiral2,5-disubstituted pyrrolidine from it.

A continuing need exists for transition metal complexes providing highlevels of stereochemical control and asymmetric induction instoichiometric and catalytic transformations. A need also exists forchiral ligands having a high degree of enantiomeric purity for use inthe preparation of transition metal catalysts, and for efficientsynthetic routes for the preparation of such chiral ligands.

It therefore an object of the present invention to provide cyclicsulfate compounds for use in preparation of chiral bis (phospholane)ligands.

It is a further object of the present invention to provide bis (primaryphosphine) compounds for use in preparation of chiral bis (phospholane)ligands.

It is a further object of the present invention to provide a novel bis(phosphonite) compound for use in preparation of a specific bis (primaryphosphine).

It is a further object of the present invention to provide eitherenantiomer of chiral phospholane ligands having a high degree ofenantiomeric purity for use in the preparation of transition metalcatalysts.

It is a further object of the present invention to provide a process forthe preparation of either enantiomer of chiral phospholane ligands.

It is a further object of the present invention to provide transitionmetal complexes which afford high levels of stereochemical control andasymmetric induction in stoichiometric and catalytic transformations.

It is a further object of the present invention to provide ahydrogenation process using the transition metal catalysts of thepresent invention.

SUMMARY OF THE INVENTION

This invention comprises novel symmetrical, chiral cyclic sulfates ofthe formula I ##STR1## wherein: R is a radical comprising alkyl,fluoroalkyl or perfluoroalkyl, each containing up to about 8 carbonatoms; aryl; substituted aryl; aralkyl; ring-substituted aralkyl; --CR'₂(CR'₂)qX(CR'₂)_(p) R';

q and p are each integers, the same or different, ranging from 1 toabout 8;

X is as defined below; and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

or where together R' and R" as defined below form a ring;

X is O, S, NR", PR", AsR", SbR", divalent aryl, divalent fused aryl,divalent 6-membered ring heterocyclic group, divalent 5-membered ringheterocyclic group, or divalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R', p, and q are as defined above;

or where together R' and R" form a ring;

provided that when R is methyl, the compound has a high degree ofenantiomeric purity.

This invention further comprises a novel bis(phosphonite) compound ofthe following formula Va: ##STR2## This compound isferrocenyl-1,1'-bis(diethylphosphonite).

This invention further comprises bis(primary phosphines) of the formulaeIIIb, IVb, Vb or VIb: ##STR3## wherein: X is O, S, NR", PR", AsR", SbR",divalent aryl, divalent fused aryl, divalent 6-membered ringheterocyclic group, divalent 5-membered ring heterocyclic group, ordivalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

q and p are each integers, the same or different, ranging from 1 toabout 8;

or where together R' and R" form a ring;

and each Y is independently hydrogen, halogen, alkyl, alkoxy, aryl,aryloxy, nitro, amino, vinyl, substituted vinyl, alkynyl or sulfonicacid, and n is an integer from 1 to 6 equal to the number ofunsubstituted aromatic ring carbons.

This invention further comprises novel chiral ligands of the formulaeII, IIIc, IVc, Vc or VIc: R1 ? ? ##STR4## wherein: R is a radicalcomprising alkyl, fluoroalkyl or perfluoroalkyl, each containing up toabout 8 carbon atoms; aryl; substituted aryl; aralkyl; ring-substitutedaralkyl; --CR'₂ (CR'₂)qX(CR'₂ )_(p) R';

q and p are each integers, the same or different, ranging from 1 toabout 8;

X is as defined below; and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

or where together R' and R" as defined below form a ring;

X is O, S, NR", PR", AsR", SbR", divalent aryl, divalent fused aryl,divalent 6-membered ring heterocyclic group, divalent 5-membered ringheterocyclic group, or divalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R', P, and q are as defined above;

or where together R' and R" form a ring; and

each Y is independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy,nitro, amino, vinyl, substituted vinyl, alkynyl, or sulfonic acid, and nis an integer from 1 to 6 equal to the number of unsubstituted aromaticring carbons.

This invention further comprises a process for the preparation of chiralligands of the above structures and others which process comprises thereaction of chiral cyclic sulfates with appropriate diphosphines in thepresence of a strong base.

This invention further comprises novel chiral catalysts wherein atransition metal, lanthanide or actinide is attached to both phosphorousatoms of a chiral ligand of structure II, IIIc, IVc, Vc and VIc above.

This invention further comprises a process for the enantioselectivehydrogenation of unsaturated substrates by hydrogen in the presence ofnovel catalysts containing chiral bis(phospholane) ligands of thestructure defined as above.

DETAILED DESCRIPTION OF THE INVENTION

For the purpose of this application, by a compound "with a high degreeof enantiomeric purity", or a compound "of high enantiomeric purity" ismeant a compound that exhibits optical activity to the extent of greaterthan or equal to about 90%, preferably, greater than or equal to about95% enantiomeric excess (abbreviated ee).

Enantiomeric excess is defined as the ratio (% R-% S)/(% R+% S), where %R is the percentage of R enantiomer and % S is the percentage of Senantiomer in a sample of optically active compound.

The present invention provides symmetric chiral 1,4-diol cyclic sulfatesof formula I. ##STR5## wherein: R is a radical comprising alkyl,fluoroalkyl or perfluoroalkyl, each containing up to about 8 carbonatoms; aryl; substituted aryl; aralkyl; ring-substituted aralkyl; --CR'₂(CR'₂)qX(CR'₂)_(p) R';

q and p are each integers, the same or different, ranging from 1 toabout 8;

X is as defined below; and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

or where together R' and R" form a ring;

X is O, S, NR", PR", AsR", SbR", divalent aryl, divalent fused aryl,divalent 6-membered ring heterocyclic group, divalent 5-membered ringheterocyclic group, or divalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R', p, and q are as defined above; or where together R' and R" form aring; provided that when R is methyl, the compound has a high degree ofenantiomeric purity.

Preferred cyclic sulfates are those wherein R is methyl, ethyl orisopropyl.

These cyclic sulfates are prepared from 1,4-diols, and are useful in thepreparation of chiral ligands having a high degree of enantiomericpurity. An example of this preparative reaction is shown in Scheme I.##STR6##

The cyclic sulfates are prepared from readily available chiral1,4-diols. The diols are reacted with thionyl chloride to afford thecorresponding 1,4-diol cyclic sulfites (not isolated) which aresubsequently oxidized to the crystalline products, symmetric 1,4-diolcyclic sulfates of formula I, by NaIO₄ and a catalytic amount of RuCl₃.The cyclic sulfates are useful in reaction with primary phosphines inthe presence of strong base to prepare chiral phospholane ligands.

This invention further comprises a novel bis(phosphonite) compound offormula Va ##STR7## which is ferrocenyl-1,1'-bis (diethylphosphonite).It is prepared by reacting diethyl chlorophosphite withdilithioferrocene in an organic solvent such as tetrahydrofuran at atemperature of from about 20° C. to about 30° C. at ambient pressure.The compound is useful in the preparation of bis(primary phosphines).

This invention further comprises bis(primary phosphines) of the formulaeIIIb, IVb, Vb, or VIb: ##STR8## wherein: X is O, S, NR", PR", AsR",SbR", divalent aryl, divalent fused aryl, divalent 6-membered ringheterocyclic group, divalent 5-membered ring heterocyclic group, ordivalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR';

p and q are each integers, the same or different, ranging from 1 toabout 8;

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms; or where together R' and R" forma ring; and

each Y is independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy,nitro, amino, vinyl, substituted vinyl, alkynyl or sulfonic acid, and nis an integer from 1 to 6 equal to the number of unsubstituted aromaticring carbons.

The bis(primary phosphines) of the present invention are useful asdirect precursors to phosphorus-containing compounds including chiralbis(phospholane) ligands.

The outlined route to bis(phospholane) ligands involves the use ofbis(primary phosphine) compounds, many of which are not available orknown. The bis(primary phosphines) are prepared by treating adimetallated aryl or alkyl compound with an excess ofdiethylchlorophosphite in an organic solvent, such as ether or THF, at atemperature of from about 20° C. to about 30° C. The resultingbis(diethylphosphonite) is then reacted with a mixture of lithiumaluminumhydride/chlorotrimethylsilane (1/1) in the same organic solvent.Yields of bis(primary phosphine) are generally high.

A specific example is shown in Scheme II. A solution of1,1'-dilithioferrocene (Davidson et al., J. Organometal. Chem., 27, 241,1971) in THF is reacted with diethylchlorophosphite (4 equivalents) inTHF to afford the corresponding 1,1'-bis(diethylphosphonite)ferrocene inhigh yield (95%). This compound is subsequently reduced with 6equivalents of a 1/1 mixture of lithium aluminumhydride andchlorotrimethylsilane (Kyba et al., Organometallics, 1, 1877, 1983) inTHF solvent to provide 1,1'-diphosphinoferrocene, again in high yield(98%). Both reactions are conducted under a N₂ or Ar atmosphere and at atemperature of from about 20° C. to about 30° C. ##STR9##

The present invention further comprises chiral bis(phospholane) ligandsof formulae II, IIIc, IVc, Vc, and VIc: ##STR10## wherein: R is aradical comprising alkyl, fluoroalkyl or perfluoroalkyl, each containingup to about 8 carbon atoms; aryl; substituted aryl; aralkyl;ring-substituted aralkyl; --CR'₂ (CR'₂)qX(CR'₂)_(p) R';

q and p are each integers, the same or different, ranging from 1 toabout 8;

X is as defined below; and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

or where together R' and R" form a ring;

X is O, S, NR", PR", AsR", SbR", divalent aryl, divalent fused aryl,divalent 6-membered ring heterocyclic group, divalent 5-membered ringheterocyclic group, or divalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R', P, and q are as defined above;

or where together R' and R" form a ring; and

each Y is independently hydrogen, halogen, alkyl, alkoxy, aryl, aryloxy,nitro, amino, vinyl, substituted vinyl, alkynyl or sulfonic acid, and nis an integer from 1 to 6 equal to the number of unsubstituted aromaticring carbons.

Preferred chiral ligands are those wherein R is methyl, ethyl, orisopropyl and Y is hydrogen. The chiral ligands of formulae II, IIIc,IVc, Vc, VIc and VII on Scheme III hereinafter are useful in thepreparation of transition metal complexes which act as catalysts.

The present invention further comprises a process for the preparation ofchiral ligands of structures II, IIIc, IVc, Vc, and VIc above, VII, andothers, which process comprises the reaction of an appropriatediphosphine with a chiral cyclic sulfate of formula I above wherein:

R is a radical comprising alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms; aryl; substituted aryl; aralkyl;ring-substituted aralkyl; --CR'₂ (CR'₂)qX(CR'₂)_(p) R';

q and p are each integers, the same or different, ranging from 1 toabout 8;

X is as defined below; and

R' is H; F; aryl; or alkyl, fluoroalkyl or perfluoroalkyl, eachcontaining up to about 8 carbon atoms;

or where together R' and R" form a ring;

X is O, S, NR", PR", AsR", SbR", divalent aryl, divalent fused aryl,divalent 6-membered ring heterocyclic group, divalent 5-membered ringheterocyclic group, or divalent fused heterocyclic group;

R" is hydrogen; alkyl, fluoroalkyl or perfluoroalkyl, each containing upto about 8 carbon atoms; aryl; substituted aryl; aralkyl; ringsubstituted aralkyl; or CR'₂ (CR'₂)qZ(CR'₂)_(p) R';

Z is O, S, NR', PR', AsR', or SbR', and

R', p, and q are as defined above;

or where together R' and R" form a ring.

Specific examples of this process are shown in Scheme III. ##STR11##

Chiral ligands are prepared by first reacting a bis(primary phosphine)or a tris(primary phosphine) with a strong base capable of deprotonatinga P--H bond. Bases such as methyl lithium, n-butyl lithium, phenyllithium, or lithium diisopropylamide, can be used to remove one protonfrom the phosphorus atom of each primary phosphine group, therebycreating an anion. This anion is then reacted with a cyclic sulfate offormula I to generate a carbon-phosphorus bond on each phosphorus. Theaddition of more strong base then removes the remaining proton from eachphosphorus and subsequently creates a heterocyclic phospholane byformation of a second carbon-phosphorus bond through sulfate groupdisplacement. The reaction is conducted in an organic solvent such astetrahydrofuran, diethyl ether or dimethoxyethane at a temperature offrom about 0° C. to the boiling point of the solvent employed. Reactionat about 20° C. to about 30° C. is preferred. An inert atmosphere isrequired, with nitrogen or argon being preferred. The reaction isconducted at ambient pressure.

Preferred for use in the process of the present invention are cyclicsulfates having a high degree of enantiomeric purity. Also preferredprocesses are those wherein R for the cyclic sulfate and resultingligands is methyl, ethyl, or isopropyl.

More specifically, as in reaction Scheme III, deprotonation of1,2-bis(phosphino)benzene (commercially available from Quantum Design,Inc., Austin, Tex.; 512-258-4174) in tetrahydrofuran is accomplishedwith n-butyllithium (2 equivalents) to give dilithium1,2-bis(phosphido)benzene. The resulting dianion is then reacted with atetrahydrofuran solution of 1,4-diol cyclic sulfate of formula I (2equivalents), followed after 1 hour, by the second addition of n-butyllithium (2.2 to 2.3 equivalents). Standard workup procedures afford thepure products, 1,2-bis(phospholano)benzenes exemplified by formula II,in good yield (80-90%). In general, the crude products obtained throughthis procedure are analytically pure and no further purification steps(i.e. distillation) are required.

By using the commercially available 1,2-bis(phosphino) ethane (QuantumDesign, Inc., Austin, Tex.; 512-258-4174), the bis(phospholano)ethanesof formula VII, previously described in U.S. Pat. No. 5,008,457, alsoare readily prepared in high yield and in pure form by this route(Scheme III). The described synthesis appears only to be limited by theavailability of the primary phosphine starting material, and can beeasily applied to the preparation of other chiral ligands such as thoseof formulae IIIc, IVc, Vc or VIc. Other phosphines of current interestare 1,1'-bis(phospholano) ferrocene of formula Vb and2,2'-bis(phospholano)binaphthyl of formula IIIb, both of which areaccessible through this synthetic route.

The great advantages of this new synthetic approach to chiralphospholanes are the experimental simplicity, high yields and productpurity (essentially enantiomerically pure products are obtained and noP--P dimer or phosphine diastereomers are ever observed), and itsamenability to increasing the scale of the preparation. Variousbis(phospholanes) previously difficult to prepare can be readilysynthesized by this route.

The present invention further comprises complexes wherein a transitionmetal, lanthanide or actinide, is attached to both phosphorus atoms ofthe chiral ligands of formulae II, IIIc, IVc, Vc, VIc or VII as definedabove. Such complexes are prepared by reacting the chiral ligand with anappropriate precursor complex. Typical precursor transition metalcomplexes suitable for use herein include, among others, [(COD)₂ Rh]⁺ X⁻wherein COD is 1,5-cyclooctadiene, and X is BF₄, SbF₆, PF₆, CF₃ SO₃ ; or[CODRu(2-methylallyl)₂ ] wherein COD is as previously defined. Thepreparation is usually conducted in an organic solvent under an inertatmosphere such as nitrogen or argon. The reaction is conducted atambient pressure at a temperature between 0° C. and the boiling point ofthe solvent. The resulting complexes containing the bis(phospholanes)have a high degree of enantiomeric purity and are useful as catalystswhich provide high enantiomeric selectivity in hydrogenation ofunsaturated substrates.

A further aspect of the present invention comprises an improved processfor hydrogenation of unsaturated substrates wherein the improvementcomprises using the complexes as described above as catalysts. Suitableunsaturated substrates include acetamidoacrylates, enol acetates such as1-acetoxy-(substituted aryl)ethylenes, itaconate esters, ketones,olefins, substituted olefins, imines, enol carbamates, andα,β-unsaturated carboxylic acids. Generally a reactor is charged withsubstrate and catalyst and optionally with solvent and pressurized withhydrogen gas. Hydrogenation can be carried out in a batch or in acontinuous manner. Hydrogen uptake is monitored. Reaction completion ismonitored by gas chromatography or nuclear magnetic resonance.

Several rhodium and ruthenium complexes containing the new chiralphospholane ligands of the present invention have been prepared and wereshown to provide very high levels of asymmetric induction inhydrogenation reactions yielding hydrogenated products having a highdegree of enantiomeric purity. For example, enantiomeric excessesapproaching 100% ee were observed in the hydrogenation of methylacetamidocinnamate, dimethyl itaconate, methyl acetamidoacrylate and2-methyl-2-butenoic acid. The rates and catalytic efficiencies (0.1 mol% catalyst) of these reactions were extremely high.

The following examples illustrate the present invention, but are notintended to limit it in any manner.

It is understood that the following procedures can be used to generateeither enantiomer of the chiral compounds listed in a high degree ofenantiomeric purity.

General Procedures

All reactions and manipulations were performed in a nitrogen-filledVacuum Atmospheres Dri-Lab glovebox or using standard Schlenk-typetechniques. Benzene, toluene, diethyl ether (Et₂ O), tetrahydrofuran(THF), glyme, hexane, and pentane were distilled fromsodium-benzophenone ketyl under nitrogen. Acetonitrile (CH₃ CN) andmethylene chloride (CH₂ Cl₂) were distilled from CaH₂. Methanol (MeOH)was distilled from Mg(OMe)₂.

Melting points were determined using a Mel-Temp apparatus in capillariessealed under nitrogen and are uncorrected. HPLC analyses were performedusing a Hewlett Packard Model HP 1090 LC interfaced to a HP 9000 Series300 computer workstation. Optical Rotations were obtained using a PerkinElmer Model 241 MC Polarimeter. NMR spectra were obtained on NicoletNT-360 wide-bore (360 MHz ¹ H 146 MHz ³¹ P), Nicolet NMC-300 wide-bore(300 MHz ¹ H, 120.5 MHz ³¹ P, 75.5 Mz ¹³ C) and Nicolet QM-300narrow-bore (300 MHz ¹ H) spectrometers. ¹³ C and ³¹ P NMR chemicalshifts are positive downfield (and negative upfield) from external Me₄Si and 85% H₃ PO₄, respectively. IR spectra were recorded on a Nicolet5DXB FT-IR spectrometer. Elemental analyses were performed by OneidaResearch Services, Inc., Whitesboro, N.Y., Schwarzkopf MicroanalyticalLaboratory, Inc., Woodside, N.Y., or Pascher Mikroanalytisches Labor,Remagen-Bandorf (FRG).

EXAMPLE 1 a) Chiral β-hydroxy esters

The preparation of chiral β-hydroxy esters used in the diol syntheseswas carried out as described by Noyori et al., J. Amer. Chem. Soc., 109,5856 (1987) which is herein incorporated by reference who have reportedthe asymmetric reduction of β-keto esters using a ruthenium catalystbearing the chiral phosphine ligand BINAP (both enantiomers commerciallyavailable from Strem Chemicals). All keto ester reductions wereconducted on a 300 g scale in Hasteloy steel autoclave vessels in aMeOH/CH₂ Cl₂ (300 mL/300 mL) solvent mixture. The reactions were allowedto proceed at constant H₂ pressure (1500 psi) for 48 h at 25° C.Complete conversion of the β-keto ester substrates was observed in allcases and the products were simply distilled from the crude reactionmixture. Consistent with the results of Noyori et al., all products weredetermined >99% enantiomerically pure.

b) Chiral β-hydroxy acids

A mixture of (3R)-methyl 3-hydroxypentanoate (290 g, 2.2 mol) in water(200 mL) and ethanol (200 mL) was cooled to 0° C. To this cold solutionwas added a solution of KOH (185 g, 3.3 mol) in water (1 L). Thereaction was then allowed to stir at 25° C. for 48 h. The resultingsolution was concentrated to ca. 500 mL and acidified (conc. HCl) untilpH=1 was reached. The precipitated salts were filtered and the filtratewas subjected to continuous liquid/liquid extraction with diethyl ether(1 L) for 24 h. The diethyl ether was removed on a rotovap to afford theproduct β-hydroxy acid as a colorless oil (250 g, 97%). The crudeproduct was sufficiently pure to use in the next step (Kolbe-coupling).

c) (2R,5R)-2,5-hexanediol

A 1000 mL jacketed reaction vessel was charged with(3R)-3-hydroxybutyric acid (52.0 g, 0.5 mol), methanol (390 mL) andsodium methoxide (110 mL of a 0.5N solution in methanol, 0.055 mol), andthe mixture (pH=5.38) was cooled to 0° C. with a circulating bath. Theelectrode configuration used consists of a Pt foil anode (20 cm²)wrapped around the outside bottom of a small jointed tube which fitinside a larger jointed tube with a Pt foil cathode (30 cm²) lining theinside (avg electrode gap=2.5 mm). Using a 30 amp DC power supply(Hewlett Packard Model No. 6269B), a constant current (current density0.25 A/cm²) of 5 amp was applied until 56,000 coulombs (1.2 F/mol) werepassed at which point complete conversion of hydroxy acid was indicatedby gas chromatography. The reaction and gas evolution (H₂ and CO₂)proceed normally until ca. 1.0 F/mol current were passed, after whichthe resistance and solution pH are observed to increase. The colorlessreaction mixture was then concentrated on a rotovap, and the resultingsolid residue was extracted EtOAc (500 mL). After filtering, theremaining solids were stirred with EtOAc (100 mL) for 10 h, filtered,and the combined EtOAc extracts (600 mL) were concentrated to acolorless solid. The solids were dissolved in a minimum amount of warmEt₂ O, quickly filtered through a coarse frit, and the filtrate cooledto -78° C. After two hours, the colorless crystals were filtered, washedwith cold pentane, and dried in vacuo (Yield 14.4 g, 48%). mp 53°-54°C.; [α]²⁵ D=-39.6°±0.50° (c 1, CHCl₃) ¹ H NMR (CD₂ Cl₂) δ1.15 (d, J_(HH)=6.2 Hz, 6H, CH₃), 1.50 (m, 4H, CH₂), 2.95 (br, 2H, OH), 3.75 (m, 2H,CH); ¹³ C NMR (CD₂ Cl₂) d 23.6, 35.9, 68.1. Anal. Calcd for C₆ H₁₄ O₂ :C, 60.98; H, 11.94. Found: C, 61.12; H, 11.64.

d) (2S,5S)-2,5-hexanediol

This compound was prepared as described in c) above except that(3S)-3-hydroxybutyric acid was used as substrate. [α]²⁵ D=+39.4°±0.5° (c1, CHCl₃). Other spectroscopic properties were identical to those givenfor the product of c) above.

e) (2R,5R)-2.5-hexanediol cyclic sulfate

To (2R,5R)-2,5-hexanediol of Example 1c) (10.0 g, 0.085 mol) in CCl₄ (60mL) was added via syringe thionyl chloride (7.75 mL, 0.106 mol). Theresulting brownish solution was then refluxed for 1.5 hour. Aftercooling to 25° C. the reaction was concentrated on a rotovap to afford abrown oil. The oil was then dissolved in a mixture of CCl₄ (60 mL), CH₃CN (60 mL), and H₂ O (90 mL) and the mixture was cooled to 0° C. To thecool mixture was added RuCl₃ trihydrate (0.12 g, 0.58 mmol) followed bysolid NaIO₄ (36.2 g, 0.169 mol). The reaction was allowed to stir at 25°C. for 1 h. At this point, H₂ O (400 mL) was added and the mixture wasextracted with diethyl ether (4×200 mL) and the combined ether extractswere washed with brine (2×100 mL). After drying over MgSO₄ andfiltration through a pad of SiO₂ (important to remove dissolved Rusalts), the colorless solution was concentrated to ca. 20 mL on arotovap. The addition of hexane (70 mL) and cooling to -10° C. affordedthe product as a colorless crystalline solid which was filtered, washedwith cold hexane and dried. Recrystallization from ether/hexane in asimilar manner yielded pure colorless crystalline product of the titlewhich is best stored below 0° C. (12.4 g, 81%): mp 80° C. (dec.); [α]²⁵D=-32.4° (cl. CHCl₃); ¹ H NMR (CDCl₃) δ1.32 (d, J_(HH) =6.5 Hz, 6H,CH₃), 1.55 (m, 2H, CH₂), 2.20 (m, 2H, CH₂), 3.60 (m, 2H, CH); ¹³ C NMR(CDCl₃) δ22.67, 39.53, 44.31; HRMS (EI, direct insert): m/z 181.0551 (M⁺+H, exact mass calcd for C₆ H₁₃ O₄ S: 181.0534), 137.0284 (M-C₂ H₃ O).

EXAMPLE 2 (3S,6S)-3,6-octanediol cyclic sulfate

To (3S,6S)-3,6-octanediol prepared as in Example 1d) (15.0 g, 0.103 mol)in CCl₄ (60 mL) was added via syringe thionyl chloride (9.4 mL, 0.128mol). The resulting brownish solution was then refluxed for 1.5 h. Aftercooling to 25° C. the reaction was concentrated on a rotovap to afford abrown oil. The oil was then dissolved in a mixture of CCl₄ (90 mL), CH₃CN (90 mL), and H₂ O (135 mL) and the mixture was cooled to 0° C. To thecool mixture was added RuCl₃ trihydrate (0.18 g, 0.87 mmol) followed bysolid NaIO₄ (44.06 g, 0.206 mol). The reaction was allowed to stir at25° C. for 1 h. At this point, H₂ O (500 mL) was added and the mixturewas extracted with diethyl ether (4×200 mL) and the combined etherextracts were washed with brine (2×100 mL). After drying over MgSO₄ andfiltration through a pad of SiO₂ (important to remove dissolved Rusalts), the colorless solution was concentrated to ca. 20 mL on arotovap. The addition of hexane (70 mL) and cooling to -10° C. affordedthe titled product as a colorless crystalline solid which was filtered,washed with cold hexane and dried. Recrystallization from ether/hexanein a similar manner yielded pure colorless crystalline product (15.1 g,71%): mp 79.5°-80.5° C.; [α]²⁵ D=+28.6° (cl. CHCl₃ ); ¹ H NMR (CDCl₃)δ0.98 (t, J_(HH) =7.2 Hz, 6H, CH₃), 1.5-1.75 (m, 6H, CH₂), 2.20 (m, 2H,CH₂), 3.35 (m, 2H, CH); ¹³ C NMR (CDCl₃) δ13.15, 30.62, 36.89, 51.34.

EXAMPLE 3 (3S,6S)-3,6-dihydroxy-2,7-dimethyloctane cyclic sulfate

To (3S,6S)-3,6-dihydroxy-2,7-dimethyloctane prepared as in Example 1d)(14.75 g, 0.085 mol) in CCl₄ (60 mL) was added via syringe thionylchloride (7.75 mL, 0.106 mol). The resulting pale yellow solution wasthen refluxed for 1.5 h After cooling to 25° C. the reaction wasconcentrated on a rotovap to afford a pale yellow oil. The oil was thendissolved in a mixture of CCl₄ (60 mL), CH₃ CN (60 mL), and H₂ O (90 mL)and the mixture was cooled to 0° C. To the cool mixture was added RuCl₃trihydrate (0.12 g, 0.58 mmol) followed by solid NaIO₄ (36.2 g, 0.169mol). The reaction was allowed to stir at 25° C. for 1 h. At this point,H₂ O (400 mL) was added and the mixture was extracted with diethyl ether(4×200 mL) and the combined ether extracts were washed with brine (2×100mL). After drying over MgSO₄ and filtration through a pad of SiO₂(important to remove dissolved Ru salts), the colorless solution wasconcentrated to dryness on a rotovap to afford a colorless crystallinematerial. Recystallization from warm hexane (25 mL) and cooling to -10°C. afforded the titled product as a colorless crystalline solid whichwas filtered, washed with cold hexane and dried (18.14 g, 90%): mp92.5°-93.5° C.; [α]²⁵ D=-55.0° (cl. CHCl₃); ¹ H NMR (CDCl₃) δ0.97 (d,J_(HH) =6.72 Hz, 6H, CH₃), 0.98 (d, J_(HH) =6.66 Hz, 6H, CH₃), 1.85 (m,2H, CH), 1.90 (m, 4H, CH₂), 4.40 (m, 2H, CH); ¹³ C NMR (CDCl₃) δ17.11,18.67, 30.01, 32.79, 89.50.

EXAMPLE 4 1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene

To 1,2-bis(phosphino)benzene (0.79 g, 5.56 mmol) in THF (100 mL) wasadded dropwise via syringe n-BuLi (6.95 mL of a 1.6M solution in hexane,2.0 equiv.). The yellow solution was allowed to stir for 1.5 h duringwhich it became slightly cloudy. To the resulting mixture was then addeda THF solution (10 mL) of (2R,5R)-2,5-hexanediol cyclic sulfate preparedas in Example 1e) (2.03 g, 11.3 mmol) upon which the reactiondecolorized. After stirring for 1 h, n-BuLi (7.65 mL of a 1.6M hexanesolution, 2.2 equiv.) was again added dropwise via syringe. Initially, ayellow color appeared and then faded, and a gelatinous precipitateformed (additional THF may be added at this point in order to maintainstirring). Toward the end of the addition the reaction remained yellow.The mixture was allowed to stir for 1.5 h, after which MeOH (3 mL) wasadded to quench any excess n-BuLi remaining. The resulting colorlessmixture was filtered, and the gelatinous precipitate was washedthoroughly with diethyl ether. The filtrate was concentrated to producea solid residue which was extracted with pentane (50 mL) and filtered.Concentration of the filtrate to 10 mL and cooling to -10° C. led to thetitled product as colorless crystals (0.80g) which were filtered anddried in vacuo. Further concentration of the filtrate andrecrystallization of the residue from MeOH at -10° C. led to a secondcrop of crystals (0.53 g) which were filtered and dried in vacuo.Combined total yield 1.33 g (78%): [α]D²⁵ =+476° (cl, hexane); ¹ H NMR(C₆ D₆) δ0.95 (ddd, 6H, CH₃), 1.24 (ddd, 6H, CH.sub. 3), 1.20-1.35 (m,2H, CH₂), 1.70 (m, 1H, CH₂), 1.95 (m, 1H, CH₂), 2.45 (m, 2H, CH), 7.05(m, 2H, Ph), 7.25 (m, 2H, Ph); ³¹ P NMR (C₆ D₆) δ+2.9; ¹³ C NMR (C₆ D₆)δ18.65, 20.66 (t, J_(CP) =18.2 Hz, CH₃), 32.89, 34.38 (t, J_(CP) =6.8Hz), 35.91, 36.49, 128.0, 131.49, 144.56; HRMS (EI, direct insert): m/z306.1638 (M⁺, exact mass calcd for C₁₈ H₂₈ P₂ : 306.1667), 223.0796(M-C₆ H₁₁), 192.1064 (M-C₆ H₁₁ P).

EXAMPLE 5 1,2-Bis((2R,5R)-2,5-diethylphospholano)benzene

To 1,2-bis(phosphino)benzene (1.01 g, 7.11 mmol) in THF (100 mL) wasadded dropwise via syringe n-BuLi (8.90 mL of a 1.6M solution in hexane,2.0 equiv.). The yellow solution was allowed to stir for 1.5 h duringwhich it became slightly cloudy. To the resulting mixture was then addeda THF solution (10 mL) of (3S,6S)-3,6-octanediol cyclic sulfate preparedas in Example 2 (3.0 g, 14.4 mmol) upon which the reaction decolorized.After stirring for 1 h, n-BuLi (9.80 mL of a 1.6M hexane solution, 2.2equiv.) was again added dropwise via syringe. Initially, a yellow colorappeared and then faded. Toward the end of the addition the reactionremained yellow. The mixture was allowed to stir for 1.5 h, after whichMeOH (3 mL) was added to quench any excess n-BuLi remaining. Theresulting colorless mixture was concentrated to produce a gelatinousresidue which was extracted with pentane (150 mL) and filtered.Concentration of the filtrate afforded the titled product as a colorlessoil (2.02 g, 78%). The crude product was essentially pure and could beused without any further purification. If further purification isdesired, the product may be distilled in vacuo: [α]D²⁵ =-265° (cl,hexane); ¹ H NMR (C₆ D₆) δ0.85 (m, 6H, CH₃), 0.80-0.90 (m, 2H, CH₂ ),0.97 (t, J_(HH) =7.3 Hz, 6H, CH₃), 1.10-1.40 (m, 4H, CH₂), 1.50-1.80 (m,6H, CH₂), 1.90 (m, 2H, CH), 2.00-2.20 (m, 4H, CH₂), 2.35 (m, 2H, CH),7.06 (m, 2H, Ph), 7.31 (m, 2H, Ph); ³¹ P NMR (C₆ D₆) δ-4.5; ³¹ C NMR (C₆D₆) δ13.99, 14.11 (d, J_(PC) =4.15 Hz), 25.37, 28.80 (t, J_(PC) =16.56Hz), 33.06, 33.37, 41.92, 42.34 (t, J_(CP) =6.70 Hz), 127.62, 132.25,144.33; HRMS (EI, direct insert): m/z 362.2245 (M⁺, exact mass calcd forC₂₂ H₃₆ P₂ : 362. 2292), 293.1570 (M-C₅ H₉), 251.1086 (M-C₈ H₁₅),216.1193 (M-C₁₁ H₁₄), 185.1395 (M-C₁₁ H₁₄ P).

EXAMPLE 6 1,2-Bis(2R,5R)-2,5-diethylphospholano)ethane

To 1,2-bis(phosphino)ethane (0.667 g, 7.10 mmol) in THF (100 mL) wasadded via syringe n-BuLi (8.90 mL of a 1.6M solution in hexane, 2.0equiv.). The pale yellow solution was allowed to stir for 1.5 h. To theresulting mixture was then added a THF solution (10 mL) of(3S,6S)-3,6-octanediol cyclic sulfate prepared as in Example 2 (3.0 g,14.4 mmol) upon which the reaction decolorized. After stirring for 1 h,n-BuLi (10.2 mL of a 1.6M hexane solution, 2.3 equiv.) was again addeddropwise via syringe. Initially, a yellow color appeared and then faded,and a gelatinous precipitate formed (additional THF may be added at thispoint in order to maintain stirring). Toward the end of the addition thereaction remained pale yellow. The mixture was allowed to stir for 1.5h, after which MeOH (3 mL) was added to quench any excess n-BuLiremaining. The resulting colorless mixture was concentrated to produce agelatinous residue which was extracted with pentane (150 mL) andfiltered. Concentration of the filtrate afforded the titled product as acolorless oil (1.92 g, 86%). The crude product was essentially pure andcould be used without any further purification. If further purificationis desired, the product may be distilled in vacuo: [α]D²⁵ =+320° (cl,hexane); ¹ H NMR (C₆ D₆) δ0.93 (t, J_(HH) =8.2 Hz, 6H, CH₃), 0.95-1.10(m, 2H, CH₂), 1.03 (t, J_(HH) =7.8 Hz, 6H, CH₃), 1.15-1.40 (m, 6H, CH₂),1.45-1.75 (m, 12H, CH₂), 1.80 (m, 2H, CH), 1.95 (m, 2H, CH); ³¹ P NMR(C₆ D₆) δ-5.9; ¹³ C NMR (C₆ D₆) δ14.75, 15.00, 20.32, 23.48, 29.46,34.13, 34.94, 43.08, 45.85; HRMS (EI, direct insert):m/z 314.2289 (M⁺,exact mass calcd for C₁₈ H₃₆ P₂ : 314.2292), 286.1949 (M-C2H4), 203.1099(M-C8H15), 172.1372 (M-C₈ H₁₅ P), 144.1037 (C₈ H₁₇ P fragment).

EXAMPLE 7 1,2-Bis((2R,5R)-2,5-diiso-propylphospholano)ethane

To 1,2-bis(phosphino)ethane (0.50 g, 5.32 mmol) in THF (75 mL) was addedvia syringe n-BuLi (6.65 mL of a 1.6M solution in hexane, 2.0 equiv.).The pale yellow solution was allowed to stir for 1.5 h. To the resultingmixture then was added a THF solution (10 mL) of(3S,6S)-3,6-dihydroxy-2,7-dimethyloctane cyclic sulfate prepared as inExample 3 (2.53 g, 10.7 mmol) upon which the reaction decolorized. Afterstirring for 1 h, n-BuLi (7.64 mL of a 1.6M hexane solution, 2.3 equiv.)was again added dropwise via syringe. Initially, a yellow color appearedand then faded, and a gelatinous precipitate formed (additional THF maybe added at this point in order to maintain stirring). Toward the end ofthe addition the reaction remained pale yellow. The mixture was allowedto stir for 1.5 h, after which MeOH (3 mL) was added to quench anyexcess n-BuLi remaining. The resulting colorless mixture wasconcentrated to produce a gelatinous residue which was extracted withpentane (150 mL) and filtered. Concentration of the filtrate to ca. 10mL and cooling to -20° C. provided the titled product as colorlesscrystals which were filtered and dried in vacuo (1.45 g, 74%). The crudeproduct was analytically pure and could be used without any furtherpurification. If further purification is desired, the product may berecrystallized from Et₂ O/MeOH at -20° C. to provide colorless crystals:[α]D²⁵ =-264°±3° (c 1, hexane); ¹ H NMR (C₆ D₆) δ0.84 (d, J_(HH) =6.4Hz, 6H, CH₃), 0.80-1.10 (m, 2H, CH₂), 0.95 (d, J_(HH) =6.6 Hz, 6H, CH₃),1.09 (d, J_(HH) =6.5 Hz, 6H, CH₃), 1.10 (d, J_(HH) =6.5 Hz, 6H, CH₃),1.20-1.45 (m, 4H, CH₂), 1.45-1.75 (m, 8H, CH, CH₂), 1.80-2.05 (m, 4H,CH); ³¹ P NMR (C₆ D₆) δ-10.1; ¹³ C NMR (C₆ D₆) δ20.27, 20.36, 22.24,22.81, 23.21, 24.52, 29.48, 32.84, 33.04, 50.32,52.19; HRMS (EI, directinsert): m/z 370.2894 (M⁺, exact mass calcd for C₂₂ H₄₄ P₂ : 370.2918),355.2603 (M-CH₃), 342.2634 (M-C₂ H₄), 327.2336 (M-C₃ H₇), 231.1241(M-C₁₀ H₁₉), 199.1611 (M-C₁₀ H₂₀ P fragment), 172.1387 (Cl₁₂ H₂₃ Pfragment).

EXAMPLE 8 1,2-Bis((2R,5R)-2,5-diiso-propylphospholano)benzene

To 1,2-bis(phosphino)benzene (1.20 g, 8.44 mmol) in THF (100 mL) wasadded dropwise via syringe n-BuLi (10.6 mL of a 1.6M solution in hexane,2.0 equiv.). The yellow solution was allowed to stir for 1.5 h duringwhich it became slightly cloudy. To the resulting mixture was then addeda THF solution (10 mL) of (3S,6S)-3,6-dihydroxy-2,7-dimethyloctanecyclic sulfate prepared as in Example 3 (4.01 g, 17.0 mmol) upon whichthe reaction decolorized. After stirring for 1 h, n-BuLi (12.15 mL of a1.6M hexane solution, 2.2 equiv.) was again added dropwise via syringe.Initially, a yellow color appeared and then faded. Toward the end of theaddition the reaction remained yellow. The mixture was allowed to stirfor 1.5 h, after which MeOH (3 mL) was added to quench any excess n-BuLiremaining. The resulting colorless mixture was concentrated to produce agelatinous residue which was extracted with pentane (150 mL) andfiltered. Concentration of the filtrate afforded the titled product as aviscous colorless oil (2.47 g, 70%). The crude product was essentiallypure and could be used without any further purification. Furtherpurification, if desired, may be accomplished by distillation in vacuo:[α]D²⁵ =+59.6°±1° (cl, hexane); ¹ H NMR (C₆ D₆) δ0.65 (d, J_(HH) =6.4Hz, 6H, CH₃), 0.80-1.10 (m, 2H, CH₂), 1.03 (d, J_(HH) =6.6 Hz, 12H,CH₃), 1.10 (d, J_(HH) =6.5 Hz, 6H, CH₃), 1.20-1.65 (m, 6H, CH₂),1.65-2.20 (m, 6H, CH, CH₂), 2.40 (m, 2H, CH), 7.00 (m, 2H, Ph), 7.40 (m,2H, Ph); ³¹ P NMR (C₆ D₆) δ-11.2; HRMS (EI, direct insert): m/z 418.2916(M⁺ , exact mass calcd for C₂₆ H₄₄ P₂ : 418.2918), 403.2633 (M-CH₃),375.2351 (M-C₃ H₇), 279.1535 (M-C₁₀ H₁₉), 247.1485 (M-C₁₀ H₂₀ Pfragment).

EXAMPLE 9 Ferrocenyl-1,1'-bis(diethylphosphonite)

To diethyl chlorophosphite (8.0 g, 0.051 mol) in THF (15 mL) was addeddropwise a THF solution of 1,1'-dilithioferrocene (4.0 g, 0.013 mol).The reaction was allowed to stir for 2 h at 25° C. after which ³¹ P NMRmonitoring indicated complete conversion to product. The reaction wasthen concentrated in vacuo, and the resulting orange residue wasextracted with pentane. After filtering through a pad of celite, thefiltrate was concentrated to give the product as a dark orange oil (5.15g, 95%): ¹ H NMR (C₆ D₆) δ1.05 (t, 3H, CH₃), 3.75 (d, 2H, CH₂), 4.25 (s(br), 2H, CpH), 4.45 (s (br), 2H, CpH); ³¹ P NMR (C₆ D₆) δ156.5.

EXAMPLE 10 1,1'-Bis(phosphino)ferrocene

To a cold (-30° C.) solution of lithium aluminumhydride (1.07 g, 28.2mmol) in THF (75 mL) is added a cold solution (-30° C.) ofchlorotrimethylsilane (3.06 g, 28.2 mmol) in THF (5 mL), and the mixtureis allowed to stir at 25° C. for 1.5 h. To the resulting mixture isadded a solution of compound prepared in Example 9,ferrocenyl-1,1'-bis(diethylphosphonite) (2.0 g, 4.7 mmol), in THF (10mL). The reaction was allowed to stir at 25° C. for 6 h, after which asolution of MeOH (5 mL) in THF (10 mL) was slowly added dropwise. Afterstirring for 1 h, the reaction was filtered and the filtrateconcentrated to dryness. The residue was extracted with diethyl ether(100 mL), filtered, and concentrated to an orange oil. The resulting oilwas dissolved in pentane, filtered, and the filtrate concentrated toafford the product as an orange oil (1.15 g, 98%): ¹ H NMR (C₆ D₆) δ3.36(t, J_(PH) =202 Hz, J_(HH) =3.3 Hz, 2H, PH), 3.92 (m, 2H, CpH), 3.96 (m,2H, CpH), 4.03 (t, J_(PH) =202 Hz, J_(HH) =3.3 Hz, 2H, PH); ³ P NMR (C₆D₆) δ-145.5 (t, J_(PH) =202 Hz); ³ C NMR (C₆ D₆) δ72.14, 76.99, 77.0 (d,J_(PC) =15.2 Hz).

EXAMPLE 11 1,1'-Bis((2R,5R)-2,5-diethylphospholano)ferrocene

To a solution of 1,1'-bis(phosphino) ferrocene (0.2 g, 0.8 mmol) in THF(30 mL) was added dropwise via syringe n-BuLi (1.0 mL of a 1.6M solutionin hexane, 2.0 equiv.). The orange solution was allowed to stir for 1.5h during which it became slightly cloudy. To the resulting mixture wasthen added a THF solution (10 mL) of (3S,6S)-3,6-octanediol cyclicsulfate (0.338 g, 1.6 mmol). After stirring for 1 h, n-BuLi (1.15 mL ofa 1.6M hexane solution, 2.2 equiv.) was again added dropwise viasyringe. The mixture was allowed to stir for 1.5 h, after which MeOH (3mL) was added to quench any excess n-BuLi remaining. The resultingorange mixture was concentrated to produce a gelatinous residue whichwas extracted with pentane (150 mL) and filtered. Concentration of thefiltrate to 5 mL and cooling to -30° C. for 10 h afforded the product asan orange crystalline solid which was filtered, washed with cold MeOHand dried (0.29 g, 77%). The crude product was essentially pure and maybe used without any further purification. ¹ H NMR (C₆ D₆) δ0.88 (m, 6H,CH₃), 0.9-1.20 (m, 4H, CH₂), 1.11 (t, J_(HH) =7.3 Hz, 6H, CH₃),1.20-1.40 (m, 4H, CH₂), 1.45-1.70 (m, 4H, CH₂), 1.70-1.90 (m, 4H, CH),2.10 (m (br), 2H, CH₂), 2.40 (m, 2H, CH), 3.90 (m, 1H, CpH), 4.25 (m,2H, CpH), 4.35 (m, 1H, CpH); ³¹ P NMR (C₆ D₆) δ-9.4; ¹³ C NMR (C₆ D₆)δ14.27 (d, J_(PC) =16.1 Hz), 14.82 (d, J_(PC) =7.9 Hz), 23.76, 30.07,30.49, 34.03, 34.34 (d, J_(PC) =4.4 Hz), 42.42 (d, J_(CP) =9.9 Hz),44.44 (d, J_(CP) =11.9 Hz), 70.88 (d, J_(CP) =6.2 Hz), 71.24, 71.96 (d,J_(CP) =7.7 Hz), 77.33 (d, J_(CP) =32.8 Hz); HRMS (EI, direct insert):m/z 470.1976 (M⁺, exact mass calcd for C₂₆ H₄₀ P₂ Fe: 470.1955),359.0485 (M-C₈ H₁₅), 328.1046 (M-C₈ H₁₅ P).

EXAMPLE 12 Ruthenium complex [(2-methylallyl)₂Ru-(1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene)]

To [(COD)Ru(2-methylallyl)₂ ] (0.104 g, 0.325 mmol) in hexane (10 mL)was added 1,2-bis((2S,5S)-2,5-dimethylphospholano)benzene prepared as inExample 4 in hexane (3 mL) and the mixture was refluxed for 12 h. Aftercooling, the reaction was concentrated to dryness and the residuedissolved in a minimum amount of diethyl ether (2-3 mL). The addition ofMeOH (10 mL) and cooling to -30° C. afforded the product as an off-whitesolid which was filtered, washed with cold MeOH, and dried in vacuo(0.124 g, 74%). ¹ H NMR (C₆ D₆) δ0.35 (dd, J_(HH) =6.9 Hz, J_(PH) =9.7Hz, 6H, CH₃), 0.70 (d, 2H), 1.20 (m, 2H) 1.30-1.50 (m, 6H, CH₂), 1.40(dd, J_(HH) =7.4 Hz, J_(PH) =17.2 Hz, 6H, CH.sub. 3), 1.65 (s, 2H, CH),1.5-2.0 (m, 4H), 2.20 (s, 6H, CH₃), 2.65 (m, 2H, CH, CH₂), 2.75 (s, 2H,CH), 7.05 (m, 2H, Ph), 7.47 (m, 2H, Ph); ³¹ P NMR (C₆ D₆) δ93.0.

EXAMPLE 13 Ruthenium complex [(2-methylallyl)₂Ru-(1,2-Bis((2R,5R)-2,5-diethylphospholano)benzene)]

This complex was prepared as described above in Example 12, with theexception that the diphospholane1,2-bis((2R,5R)-2,5-diethylphospholano)benzene prepared as in Example 5was used. Recrystallization of the product from diethyl ether/methanolat -30° C. afforded the product as an off-white solid which wasfiltered, washed with cold MeOH, and dried in vacuo. ¹ H NMR (C₆ D₆)δ0.5 (t, J_(HH) =6.7 Hz, 6H, CH₃), 0.5-1.7 (m, 16H), 1.45 (t, J_(HH)=7.4 Hz, 6H, CH₃), 1.65 (s, 2H, CH), 1.7-2.2 (m, 6H), 2.20 (s, 6H, CH₃),2.40 (m, 2H, CH, CH₂), 2.75 (s, 1H, CH), 7.05 (m, 2H, Ph), 7.50 (m, 2H,Ph); ³¹ P NMR (C₆ D₆) δ91.8.

EXAMPLE 14 Ruthenium complex [(2-methylallyl)₂Ru-(1,2-Bis((2R,5R)-2,5-diisopropylphospholano)ethane)]

This complex was prepared as described above in Example 12, with theexception that the diphospholane1,2-bis((2R,5R)-2,5-diisopropylphospholano)ethane prepared as in Example7 was used. Recrystallization of the product from diethyl ether/methanolat -30° C. afforded the product as an off-white solid which wasfiltered, washed with cold MeOH, and dried in vacuo. ¹ H NMR (C₆ D₆)δ0.74 (d, J_(HH) =6.8 Hz, 6H, CH₃), 0.80-1.30 (m, 12H, CH₂), 0.81 (d,J_(HH) =6.6 Hz, 6H, CH₃), 0.95 (d, J_(HH) =6.8 Hz, 6H, CH₃), 0.98 (d,J_(HH) =6.8 Hz, 6H, CH₃), 1.40 (br, 2H, CH₂), 1.50-1.75 (m, 6H, CH,CH₂), 1.95 (m, 2H, CH), 2.10 (s, 6H, CH₃), 2.15 (s, 2 H), 2.50 (br, 4H);³¹ P NMR (C₆ D₆) δ87.4.

EXAMPLE 15 Rhodium complex[(COD)Rh(1,2-Bis((2R,5R)-2,5-diethylphospholano)benzene)]⁺ CF₃ SO₃ ⁻

To [(COD)₂ Rh]⁺ CF₃ SO₃ - (0.13 g, 0.28 mmol, COD=1,5-cyclooctadiene) inTHF (10 mL) at 25° C. was added dropwise a solution of1,2-Bis((2R,5R)-2,5-diethylphospholano)-benzene prepared as in Example 5(0.10 g, 0.28 mmol) in THF (5 mL). The solution turned orange fromyellow upon the phosphine addition. The reaction was allowed to stir for15 min, and then Et₂ O (30 mL) was slowly added to the solution toproduce an orange microcrystalline precipitate which was filtered,washed with Et₂ O, and briefly dried. The solids were dissolved in CH₂Cl₂ (5 mL), filtered, and Et₂ O (30 mL) was added slowly to the orangefiltrate to provide the titled product as an orange microcrystallinesolid (0.112 g, 56%): ¹ H NMR (CD₂ Cl₂) δ0.86 (t, J_(HH) =7.3 Hz, 6H,CH₃), 1.02 (t, J_(HH) =7.3 Hz, 6H, CH₃), 1.2-1.6 (m, 6H, CH₂), 1.85 (m,4H, CH, CH₂), 2.20 (m, 2H, CH, CH₂), 2.20-2.70 (m, 14H, CH₂, CH), 4.90(m (br), 2H, COD-CH), 5.60 (m (br), 2H, COD-CH), 7.70 (m, 4H, Ph); ³¹ PNMR (CD₂ Cl₂) δ69.5 (d, J_(RhP) =148.3 Hz).

EXAMPLE 16 Rhodium complex[(COD)Rh(1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene)]⁺ CF₃ SO₃ ⁻

This complex was prepared in a manner analogous to that described abovein Example 15 with the exception that the diphospholane1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene was used. ¹ H NMR (CD₂Cl₂) δ1.01 (dd, J_(HH) =6.8 Hz, J_(PH) =15.0 Hz, 6H, CH₃), 1.45 (dd,J_(HH) =7.1 Hz, J_(PH) =18.2 Hz, 6H, CH₃), 1.55 (m, 2H, CH₂), 1.95 (m,2H, CH, CH₂), 2.20-2.60 (m, 12H, CH₂, CH), 2.65 (m, 2H, CH, CH₂), 2.75(m, 2H, CH, CH₂), 5.05 (br, 2H, COD-CH), 5.62 (br, 2H, COD-CH), 7.75 (m,4H, Ph); ³¹ P NMR (CD₂ Cl₂) δ76.3 (d, J_(RhP) =148.7 Hz).

EXAMPLE 17 Rhodium complex [(COD)Rh(1,2-Bis((2R,5R)-2,5-diisopropylphospholano)benzene)]⁺ CF₃ SO₃ ⁻

This complex was prepared in a manner analogous to that described abovein Example 15 with the exception that the diphospholane1,2-Bis((2R,5R)-2,5-diisopropylphospholano)benzene was used. ¹ H NMR(CD₂ Cl₂) δ0.72 (d, J_(HH) =6.6 Hz, 6H, CH₃), 0.73 (d, J_(HH) =6.7 Hz,6H, CH₃), 1.13 (d, J_(HH) =6.5 Hz, 6H, CH₃), 1.14 (d, J_(HH) =6.6 Hz,6H, CH₃), 1.60 (m, 4H, CH₂), 1.95 (m, 4H, CH, CH₂), 2.15 (m, 2H, CH₂),2.20-2.45 (m, 6H, CH₂, CH), 2.45-2.70 (m, 8H, CH, CH₂), 4.95 (br, 2H,COD-CH), 5.60 (br, 2H, COD-CH), 7.65 (m, 2H, Ph), 7.75 (m, 2H, Ph); ³¹ PNMR (CD₂ Cl₂) δ65.5 (d, J_(RhP) =148.5 Hz).

EXAMPLE 18 Rhodium complex[(COD)Rh(1,2-Bis((2R,5R)-2,5-diisopropylphospholano)ethane)]⁺ CF₃ SO₃ ⁻

This complex was prepared in a manner analogous to that described abovein Example 15 with the exception that the diphospholane1,2-Bis((2R,5R)-2,5-diisopropylphospholano)ethane was used. ¹ H NMR (CD₂Cl₂) δ0.97 (d, J_(HH) =6.6 Hz, 6H, CH₃), 0.90-1.20 (m, 2H, CH₂), 1.10(d, J_(HH) =6.6 Hz, 6H, CH₃), 1.15 (d, J_(HH) =6.5 Hz, 6H, CH₃), 1.40(d, J_(HH) =6.5 Hz, 6H, CH₃), 1.30-1.50 (m, 4H, CH₂ ), 1.50-2.00 (m,10H, CH, CH₂ ), 2.00-2.60 (m, 12H, CH), 4.85 (m (br), 2H, COD-CH), 5.30(m (br), 2H, COD-CH); ³¹ P NMR (CD₂ Cl₂) δ65.2 (d, J_(RhP) =145.2 Hz).

EXAMPLE 19 Rhodium complex [(COD)Rh(1,2-Bis((2R,5R)-2,5-diethylphospholano)ethane)]⁺ CF₃ SO₃ ⁻

This complex was prepared in an analogous manner to that described aboveas in Example 15. ¹ H NMR (CD₂ Cl₂) δ1.07 (t, J_(HH) =7.3 Hz, 6H, CH₃),1.13 (t, J_(HH) =7.3 Hz, 6H, CH₃), 1.20-1.50 (m, 8H, CH₂), 1.50-2.10 (m,12H, CH, CH₂), 2.15-2.60 (m, 12H, CH, CH₂), 4.85 (m (br), 2H, COD-CH),5.30 (m (br), 2H, COD-CH), 7.70 (m, 4H, Ph); ³¹ P NMR (CD₂ Cl₂) δ71.2(d, J_(RhP) =145.3 Hz).

EXAMPLE 20 Asymmetric Hydrogenations: General Procedure

In a dry box, a 100 mL Fisher-Porter tube was charged with 0.25-0.35Mmethanol solution of substrate, anhydrous, degassed MeOH or THF (20 mL),and catalyst precursor (0.1 mol %). After four vacuum/H₂ cycles, thetube was pressurized to an initial pressure of 30 psig H₂ (Matheson,99.998%). The reactions were allowed to stir at 20°-25° C. until nofurther hydrogen uptake was observed. Complete (100%) conversion toproduct was indicated by GC and ¹ H NMR analyses, unless otherwisenoted. Reaction time for complete (100%) conversion was 1-2 h. Thereactions were concentrated, and the residue passed through a short SiO₂column (EtOAC/hexane or Et₂ O/pentane, 50/50) to afford the products.Product absolute configurations were established by sign of opticalrotations.

Enantiomeric Excess Determinations

Enantiomeric excesses listed are the average value obtained from 2-3experiments. Enantiomeric excesses were determined as follows:N-acetylphenylalanine methyl ester (HPLC, Daicel Chiralcel OJ, 1.0mL/min, 10% 2-PrOH/hexane) (R) t₁ 8.9 rain; (S) t₂ 11.4 min); N-methylester (Capillary GC, Chrompack XE-60-S-Valine-S-α-phenyl-ethylamide,155° C. isothermal) (R) t₁ 10.69 min, (S) t₂ 11.21 min; N-acetylleucinemethyl ester (Capillary GC, ChrompackXE-60-S-Valine-S-α-phenyl-ethylamide, 160° C. isothermal) (R) t₁ 16.49rain, (S) t₂ 17.48 min; N-benzoylphenylalanine methyl ester (HPLC,Daicel Chiralcel OJ, 1.0 mL/min, 10% 2-PrOH/hexane) (R) t₁ 10.1 min; (S)t₂ 13.4 min); dimethyl 2-methylsuccinate (500 MHz¹ H NMR in CDCl₃,chiral shift reagent (+)-Eu(hfc)₃), baseline resolution of estermethoxyl resonance at δ3.69 observed at Δδ 0.25;1-acetoxy-l-phenylethane derivatives (Capillary GC, J & W Cyclodex-B):Ph=C₆ H₅ (160° C. isothermal) (S) t₁ 7.66 min, (R) t₂ 7.92 min; Ph=p-FC₆H₄ (120° C. isothermal) t₁ 7.89 min, t₂ 8.15 min; Ph=m-FC₆ H₄ (120° C.isothermal) t₁ 7.33 min, t₂ 7.61 min; Ph=m-ClC₆ H₄ (130° C. isothermal)t₁ 12.44 min, t₂ 12.80 min; Ph=p-NO₂ C₆ H₄ (500 MHz¹ H NMR in CDCl₃,chiral shift reagent (+)-Eu(hfc)₃), baseline resolution of acetoxymethyl resonance at δ2.15 observed at Δδ1.2;1-acetoxy-1-(1-naphthyl)ethane (HPLC on alcohol obtained by hydrolysiswith NaOMe/MeOH, Daicel Chiralcel OJ, 1.0 mL/min, 10% 2-PrOH/hexane) t₁9.48 min, t₂ 13.53 min; ethyl O-acetyllactate (by comparison withoptical rotation of authentic product (S)-(-)-O-Acetyllactate [α]D²⁵=-50.6° (c 1.0, CHCl₃); combined with ¹ H NMR to assure reductionproduct purity); 1,1, 1-trifluoro-2-acetoxypropane (500 MHz¹ H NMR inCDCl₃, chiral shift reagent (+)-Eu(hfc)₃), baseline resolution ofacetoxy methyl resonance at δ1.60 observed at Δδ0.6.

Absolute Configurations

Hydrogenation product absolute configurations were established bycomparison of the sign of optical rotation with that of theconfigurationally assigned compound. The following referenced compoundswere used for comparison: (S)-N-acetylphenylalanine methyl ester ([α]D²⁰=+16.4° (c 2, MeOH); (S)-N-acetylalanine methyl ester ([α]D²³ =-91.7° (c2, H₂ O); (S)-N-acetylleucine methyl ester ([α]D¹⁷ =-42.0° (c 3.3,MeOH); (S)-N-benzoylphenylalanine methyl ester ([α]D²⁵ =-45.3° (c 1,MeOH); (R)-dimethyl 2-methylsuccinate ([α]D²⁵ =+6.11° (neat);(S)-1-acetoxy-1-phenylethane ([α]D²¹ =-130.5° (c 3, benzene);(R)-(+)-1-acetoxy-1-(p-nitrophenyl)ethane;(S)-1-hydroxy-1-(1-naphthyl)ethane ([α]D²¹ =-78.9° (c 5, EtOH); ethylO-acetyllactate (by comparison with optical rotation of authenticproduct (S)-(-)-O-Acetyllactate [α]D²⁵ =-50.6° (c 1.0, CHCl₃);(S)-1,1,1-trifluoro-2-acetoxypropane ([α]D²³ =+18.7° (neat)¹⁴ ;

Asymmetric Hydrogenation of

Methyl (Z)-α-acetamidocinnamate

A 100 mL Fisher-Porter tube was charged with methyl(Z)-α-acetamidocinnamate (300 mg, 1.36 mmol), rhodium catalyst[(COD)Rh(1,2-Bis((2R,5R)-2,5-diethylphospholano)benzene)]⁺ CF₃ SO₃ ⁻prepared as in Example 15 (1.0 mg, 0.00136 mmol), MeOH (6.0 mL), and astir bar. After sealing, the pressure head was then connected to ahydrogen tank (Matheson, 99.998%) and the lines were purged of air byfour vacuum/H₂ cycles. After two vacuum/H₂ cycles on the reactionmixture, the tube was pressurized to an initial pressure of 30 psig H₂.The reaction was allowed to stir at 20° C. for 2 h after which nofurther H₂ uptake was observed. Complete conversion to product wasindicated by capillary GC (methyl silicone column). The reaction wasconcentrated on a rotovap and the residue was chromatographed on a shortSiO₂ column (ca. 6×0.5 cm) using 80% ethyl acetate/hexane as eluent. Thefractions containing product were concentrated on a rotovap to givemethyl (R)-N-acetylphenylalanine as a colorless crystalline solid (270mg, 90%). Enantiomeric excess analysis by HPLC using Daicel Chiralcel OJcolumn as described above indicated 99% enantiomeric purity. Othersubstrates were hydrogenated using the above procedure and the resultingdata is summarized in Tables 1 and 2.

                  TARLE 1                                                         ______________________________________                                        Asymmetric Hydrogenation of Acetamidoacrylates                                (% ee)                                                                        Substrate                                                                      plexesCom-                                                                          ##STR12##                                                                                   ##STR13##                                                                                   ##STR14##                                  ______________________________________                                        A.sup.a                                                                             85            64.4          91.4                                        Exam- 93            81.2          98.1                                        ple 19                                                                        Exam- 93            98.8          96.4                                        ple 18                                                                        Exam- 98            95.2          99.0                                        ple 16                                                                        Exam- 99            99.0          99.4                                        ple 15                                                                        Exam- 87            96.9          95.4                                        ple 17                                                                        ______________________________________                                         .sup.a Sample A represents a ligand of high enantiomeric purity of formul     VII wherein R is methyl complexed with [(COD).sub.2 Rh].sup.+ CF.sub.3        SO.sub.3.sup.-  using the process of Example 15.                         

                  TABLE 2                                                         ______________________________________                                        Asymmetric Hydrogenation of Enol Acetates                                      ##STR15##                                                                                         Previous   % ee                                          R          Complexes Best.sup.a (configuration)                               ______________________________________                                        C.sub.6 H.sub.5                                                                          Example 16                                                                              64          89 (-)-(S)                                   p-NO.sub.2 C.sub.6 H.sub.4                                                               Example 19                                                                              65          90 (+)-(R)                                   m-ClC.sub.6 H.sub.4                                                                      Example 15                                                                              --          91 (+).sup.b                                 p-FC.sub.6 H.sub.4                                                                       Example 19                                                                              --          89 (+).sup.b                                 m-FC.sub.6 H.sub.4                                                                       Example 15                                                                              --          89 (+).sup.b                                 1-Naphthyl Example 19                                                                              --          94 (+)-(R)                                   1-Naphthyl Example 16                                                                              --          93 (-)-(S)                                   CO.sub.2 Et                                                                              Example 16                                                                              89          99 (-)-(S)                                   CO.sub.2 Et                                                                              Example 15                                                                              89         >99 (+)-(R)                                   CO.sub.2 Et                                                                              Example 19                                                                              89         >99 (+)-(R)                                   CF.sub.3   Example 16                                                                              77          94 (+ )-(S)                                  CF.sub.3   Example 19                                                                              77         >95 (-)-(R)                                   ______________________________________                                         .sup.a Values listed denote highest ee's previously reported for catalyti     asymmetric hydrogenation of these substrates in Koenig, K. E.; Bachman, G     L.; Vineyard, B. D., J. Org. Chem., 1980, 45, 2362, and Selke, R.;            Pracejus, H., J. Mol. Cat., 1986, 37,213.                                     .sup.b Absolute configuration not established.                           

EXAMPLE 21 Ruthenium-catalyzed asymmetric hydrogenation of2-methyl-2-butenoic acid

The hydrogenation of 2-methyl-2-butenoic acid was carried out in aFisher-Porter tube at 20°-25° C. in 0.67M methanol solutions ofsubstrate under initial hydrogen pressure 60 psi (4 atm). The catalystwas prepared in situ by reacting the precursor complex[(COD)Ru(2-methylallyl)₂ ] (Lewis et al., J. Chem. Soc., Dalton, 1974,951; Powell and Shaw, J. Chem. Soc. (A), 1968, 159) each hereinincorporated by reference, with 1.1 equivalents of phosphine in diethylether solution. An aliquot of this preformed catalyst solution was thenadded directly to a methanol solution of 2-methyl-2-butenoic acid, andthe mixture then placed under hydrogen pressure. The reactions wereallowed to stir for 12 h, after which no further hydrogen uptake wasobserved. Product isolation and enantiomeric excess determination wascarried out as described below.

To a solution of [(COD)Ru(2-methylallyl)₂ ] (10 mg, 0.031 mmol) indiethyl ether (0.5 mL) was added a solution of1,2-bis((2R,5R)-2,5-diisopropylphospholano)benzene (15 mg, 0,035 mmol)in diethyl ether (0.5 mL). A Fisher-Porter tube was charged with a stirbar, methanol (6.0 mL), 2-methyl-2-butenoic acid (0.4 g, 4.0 mmol), and0.1 mL of the catalyst solution prepared above in diethyl ether. Aftersealing, the pressure head was then connected to a hydrogen tank(Matheson, 99.998%) and the lines were purged of air by four vacuum/H₂cycles. After two vacuum/H₂ cycles on the reaction mixture, the tube waspressurized to an initial pressure of 60 psig H₂. The reaction wasallowed to stir at 20° C. for 12 h after which no further H₂ uptake wasobserved. Complete conversion to product was indicated by capillary GC(methyl silicone column). The reaction was concentrated on a rotovap andthe residue was dissolved in methylene chloride (20 mL). The organiclayer was then extracted once with 1N sodium hydroxide solution. Ifnecessary, the aqueous layer was filtered. The aqueous layer then wasacidified with concentrated HCl to pH=1. The resulting mixture wasextracted with diethyl ether (3×30 mL) and the organic layer dried overmagnesium sulfate. Filtration and concentration on a rotovap providedthe product, (S)-(+)-2-methylbutanoic acid, as a colorless oil (0.35 g,88%). The enantiomeric excess was determined by comparison of theobtained optical rotation with that of authentic(S)-(+)-2-methylbutanoic acid ([α]D²⁵ =+19.9° (c 1, hexane)). Observed[α]D²⁵ =+18.6° (c 1, hexane) which indicated an enantiomeric excess of93% ee. Hydrogenations of 2-methyl-2-butenoic acid using catalystsderived from other phosphines were carried out in an analogous fashion.Data are summarized in Table 3.

                  TABLE 3                                                         ______________________________________                                        Ruthenium-catalyzed Asymmetric                                                Hydrogenation of 2-Methyl-2-butenoic acid                                      ##STR16##                                                                    Ligand        % ee                                                            ______________________________________                                        Example 4     78% ee (S)                                                      Example 5     88% ee (R)                                                      Example 8     93% ee (S)                                                      ______________________________________                                    

What is claimed is:
 1. A process for the preparation of a chiral ligandof formulae II, IIIc, IVc, Vc, VIc or VII: ##STR17## wherein: R is analkyl, fluoroalkyl or perfluoroalkyl, each containing up to about 8carbon atoms; aryl; substituted aryl; aralkyl; andeach Y isindependently hydrogen, halogen, alkyl, alkoxy, nitro, amino, vinyl,substituted vinyl, alkynyl or sulfonic acid, and n is an integer from 1to 6 equal to the number of unsubstituted aromatic ringcarbons,comprising reacting a bis(primary phosphine) in the presence ofa strong base with a cyclic sulfate compound of formula I: ##STR18##wherein: R is defined as above.
 2. The process of claim 1 conducted intetrahydrofuran as a solvent.
 3. The process of claim 1 conducted atabout 20° C. to about 30° C.
 4. The process of claim 1 conducted in aninert atmosphere.
 5. The process of claim 1 wherein the cyclic sulfatehas a high degree of enantiomeric purity.
 6. The process of claim 1wherein the chiral ligands have a high degree of enantiomeric purity. 7.The process of claim 1 wherein R is methyl.
 8. The process of claim 1wherein R is ethyl.
 9. The process of claim 1 wherein R is isopropyl.